Study of the Efficacy of Cysteine Protease Inhibitors Alone or Combined with Praziquantel as Chemotherapy for Mice Schistosomiasis mansoni

Authors: Farid A., Ismail A., Rabee I., Zalat R. El Amir A.

Abstract:

This study was designed for assessment of 3 types of Cysteine protease inhibitors (CPIs) fluromethylketone (FMK), vinyl sulfone (VS) and sodium nitro prussid (SNP), to define which of them is the best for curing S. mansoni infection in mice? In vitro, treated S. mansoni adult worms recorded a mortality rate after 1 hr of exposure to 500 ppm of FMK, VS and SNP as 75, 70 and 60%, respectively. FMK+PZQ treatment recorded the maximum reduction in worm burden (97.2% at 5 wk PI). VS treatment alone or combined with PZQ increases IgM, total IgG, IgG2 and IgG4 levels. In EM study, the completely implanted spines were reported in the degenerated tegument of adult worms in all groups treated with CPIs. VS+PZQ Treatment increased Igs levels but, its effect was different on worm reduction. So, it is not enough to eliminate the infection and FMK+PZQ considered the antischistosomicidal drug of choice.

Keywords: Praziquantel, fluromethylketone, vinyl sulfone, sodium nitro prussid.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1089455

References:

[1] P. J. Hotez, D. A. P. Bundy, and K. Beegle, Helminth infections: soil-transmitted helminth infections and schistosomiasis. Disease Control Priorities in Developing Countries. Washington, DC, USA: World Bank, 2006, 2nd edition, ch. 24.
[2] Y. Osada, and T. Kanazawa, "Schistosome: its benefit and harm in patients suffering from concomitant diseases,” Hindawi Publishing Corporation Journal of Biomedicine and Biotechnology Volume 2011, Article ID 264173, 10 pages Department of Immunology and Parasitology, University of Occupational and Environmental Health, Kitakyushu 807-8555, 2011.
[3] S. Mitchell, and M. Pagano, "Pooled Testing for Effective Estimation of the Prevalence of Schistosoma mansoni,” Am. J. Trop. Med. Hyg., vol. 87, pp. 850-861, 2012.
[4] J. J. Van Hellemond, K. Retra, J. F. H. M. Brouwers, B. W. M. van Balkom, M. Yazdanbakhsh, C. B. Shoemaker, and A. G. M. Tielens, "Functions of the tegument of schistosomes: clues from the proteome and lipidome,” Int. J. Parasitol., vol. 36, pp. 691-699, 2006.
[5] C. Lengeler, J. Utzinger, and M. Tanner, "Questionnaires for rapid screening of Schistosomiasis in sub-Saharan Africa,” Bull. WHO, vol. 80, pp. 235-242, 2002.
[6] R. Ndyomugyenyi, and J. M. Minjas, "Urinary Schistosomiasis in schoolchildren in Dar-es-salam, Tanzania and the factors influcing its transmission,” Ann. Trop. Med. Parasitol., vol. 95, pp. 697-706, 2001.
[7] B. L. Cline, and B. S. Hewlett, "Community-based approach to Schistosomiasis control,” Acta. Trop. Vol. 61, pp. 107-119, 1996.
[8] I. A. Ettoum, A. M. Saad, B. M. Ismail, M. M. Ali, S. Sulaiman, J. L. Bennett, and M. R. Homeida, "Efficacy of treatment in patients with advanced hepatic fibrosis,” Am. J. Trop. Med. Hyg., vol. 48, pp. 77-81, 1993.
[9] G. R. Olds, and S. Dasarathy, "Schistosomiasis Current treatment options,” Infected Dis., vol. 2, pp. 88-99, 2000.
[10] N. R. Bergquist, "Schistosomiasis: from risk assessment to control,” Trends Parasitol., vol. 18, pp. 309–314, 2002.
[11] D. Engels, L. Chitsulo, Montresor, and L. Savioli, "The global epidemiological situation of schistosomisais and new approaches to control and research,” Acta. Tropica., vol. 82, pp. 139-146, 2002.
[12] N. D. Rawlings, and A. J. Barrett, "Evolutionary families of peptidases,” Biochem. J., vol. 290, pp. 205-218, 1993.
[13] L. Thomas, R. Leduc, B. A. Thorne, S. P. Smeekens, D. F. Steiner, and G. Thomas, "α1-Antitrypsin Portland, a bioengineered serpin highly selective for furin: Application as an ntipathogenic agent,” Proc. Natl. Acad. Sci. USA, vol. 82, pp. 5297- 5301, 1991.
[14] R. L. Cohen, X. P. Xi, C. W. Crowley, B. K. Lucas, A. D. Levinson, and M. A. Shuman, "Effects of urokinase occupancy on plasmin generation and proteolysis of basement membrane by human tumor cells,” Blood, vol. 72, pp. 479- 487, 1991.
[15] A. J. Barrett, N. D. Rawlings, and J. F. Woessner, "Handbook of proteolytic enzymes,” Acaemic Press, London and San Dieg, 1998.
[16] M.M. Ismail, S. A. Taha, A. Farghally, and A. S. El-Zony, "Laboratory induced resistance to praziquantel in experimental Schistosomiasis,” J. Egypt Soc. Parasitol., vol. 24, pp. 685-695, 1996.
[17] M. J. Doenhoff, R. G. Stanley, K. Griffiths, and C. K. Jackson, "An anti-atherogenic effect of S. mansoni infection in mice associated with a parasite- induced lowering of blood total cholesterol,” Parasitology, vol. 125, pp. 415-421, 2002.
[18] J. Utzinger, S. Xiao, M. Tanner, and J. Keiser, "Artemisinins for schistosomiasis and beyond,” Cur. Opin. Investing Drugs, vol. 8, pp. 105-116, 2007.
[19] Z. H. Fahmy, and A. M. Helmy, "Assesment of cysteine protease in Schistosomiasis and haematolgical parasitogical role of its inhibitor in the control of the disease,” The Egyptian J. of Medicine, vol. 39, pp. 1-7, 2007.
[20] M. H. Abdulla, K. C. Lim, M. Sajid, J. H. Mckerrow, and C. R. Caffrey, "Schistosomiasis mansoni: Novel chemotherapy using a cysteine protease inhibitor,” Plos. Medicine, vol. 4, pp. 130-138, 2007.
[21] T. K. Yoles, D. V. Moore, D. De Guisti, C. L. Ripsam, and H. E. Meleney, " A technique for perfusion of laboratory animals for the recovery of Schistosomes,” J. Parasitol., vol. 33, pp. 491-426, 1974.
[22] E. Engvall, and P. Perlman, "Enzyme Linked Immuno Sorbent Assay, quantitative assay of Ig G,” J. Immunochem., vol. 8, pp. 871-874, 1971.
[23] J. A. Grimaud, M. Druget, S. Peyrol, and D. Chevalier, "Collagen immunotyping in human liver: Light and electron microscope study,” J. Histochem. Cytol.,vol. 28, pp. 1145-1151, 1980.
[24] J. Utzinger, J. Keiser, X. Shuhua, M. Tanner, and B. H. Singer, "Combination chemotherapy of schistosomiasis in laboratory studies and clinical trials,” Antimicrobial Agents and Chemotherapy, vol. 47, pp. 1487-1495, 2003.
[25] T. K. Van Den Berg, H. Honing, N. Frank, Van Remoortere, W. E. Schiphorst, F. T. Liu, A. M. Deeler, R. D. Commings, C. H. Hokke, and I. Van Die, "Lacdi NAc-glycans constitute a parasite pattern for galictin-3- mediated immune recognition,” J. Immunol., vol. 173, pp. 102-1907, 2004.
[26] J. H. McKerrow, Development of cysteine protease inhibitors as chemotherapy for parasitic disease. Insights on safety, target validation, and on mechanism of action, department of pathology and pharmaceutical chemistry, UCSF VA medical center, San Francisco, CA 1999.
[27] J. C. Engel, P. S. Doyle, I. Hsieh, and J. H. Meckerrow, "Cysteine protease inhibitors cure an experimental Tryponosoma cruzi infection,” J. Exp. Med., vol. 188, 725-734, 1998.
[28] M. V. Padma, M. Behari, N. K. Misra, and G. Ahuja, "Albendazole in neurocysticercosis,” Natl. Med. J. India, vol. 8, pp. 255-258, 1995.
[29] J. E. Olson, G. K. Lee, A. Semenov, and P. J. Rosenthal, "Antimalarial effects in mice of orally administered peptidyl cysteine protease inhibitors,” Bioorganic & Medicinal chemistry, vol. 7, pp. 633-638, 1999.
[30] J. Utzinger, S. Xiao, J. Keiser, M. Chen, J. Zheng, and M. Tanner, "Current progress in the development and use of artemether for chemoprophylaxis of major human schistosome parasites,” Curr. Med. Chem., vol. 8, pp. 1841-1860, 2001.
[31] J. Utzinger, S. Xiao, K. N. N’Goran, R. Bergquist, and M. Tanner, "The potential of artemether for the control of Schistosomiasis,” Int. J. Parasitol., vol. 31, pp. 1549-1562, 2001.
[32] S. H. Xiao, M. Booth, and M. Tanner, "The prophylactic effects of artemether against Schitosoma Japonicum infections,” Parasitol. Today, vol.16, pp. 122-126, 2000.
[33] M. R. Mahmoud, and S. S. Botros, "Artemether as adjuvant therapy to praziquantel in Egyptian murine Schistosomiasis mansoni,” J. Parasitol., vol. 91, pp. 175-178, 2005.
[34] M.M. Helmy, Z. H. Fahmy, and H. Y. Sabry, " Fasciola gigantica: evaluation of the effect of phenyl vinyl sulfone in vitro,” Exp. Parasitol., vol. 119, pp. 125-134, 2008.
[35] E. R. Copo, S. L. Reed, and L. B. Corbeil, "Effect of vinyl sulfone inhibitors of cysteine proteinases on Tritrichomonas foetus infection,” J. Antimicrobial. Agents, vol. 39, pp. 259-262, 2012.
[36] S. Z. Lescana, P. P. Chieffi, R. R. Canhassi, M. Boulos, and Neto, "Antischistosomal activity of artemether in experimental schitosomiasis mansoni,” Rev. Sauad Public, vol. 38, pp. 71-75, 2004.
[37] J. K. A. L. Neves, M. D. C. A. de Lima, and V. R. A. Pereira, "Antischistosomal action of thioxoimidazolidine compounds: an ultrastructural and cytotoxicity study,” Experimental Parasitology, vol. 128, pp. 82-90, 2011.
[38] A. C. da Silva, J. K. Neves, J. I. Irmão, V. M. Costa, V. M. Souza, P. L. de Medeiros, E. C. da Silva, C. de Lima Mdo, R. Pitta Ida, M. C. Albuquerque, and S. L. Galdino, "Study of the activity of 3-benzyl-5-(4-chloro-arylazo)-4-thioxo-imidazolidin-2-one against Schistosomiasis mansoni in mice,” vol. 2012, pp. 1-8, 2012.
[39] S. M. Allegretti, R. N. de Oliveira, T. F. Frezza, and V. L. G. Rehder, "The use of Brazillian medicinal plants to combat S. mansoni,” Schistosomiasis, Prof. Mohammad Bagher Rokni (Ed.), ISBN: 978-953-307-852-6, 2012.
[40] N. D. Gamboa de Domingues, and P. J. Rosenthal, "Cysteine proteinase inhibitors block early steps in hemoglobin degradation by cultured malaria parasites,” Blood, vol. 87, pp. 4448-4454, 1996.
[41] M. G. R. Pitta, A. C. A. Silva, and J. K. A. L. Neves, "New imidazolidinic biososters: potential candidates for antischistosomal drugs,” Memorias do Instituto Oswaldo Cruz, vol. 101, pp. 313-316, 2006.
[42] J. Utzinger, and J. Keiser, "Schistosomiasis and soil-transmitted helminthiasis: common drugs for treatment and control,” Expert Opinion on Pharmacotherapy,vol. 5, pp. 263-285, 2004.
[43] I. Rabia, F. Nagy, E. Aly, A. Mohamed, F. El-Assal, and A. El-Amir, "Effect of treatment with antifibrotic drugs in combination with PZQ in immunized S. mansoni infected murine model,” The journal of American Science, vol. 6, pp. 208-216, 2010
[44] F. N. Boctor, and J. P. Peter, "IgG subclasses in human chronic Schistosomiasis: Over-production of Schistosome-specis and non-specific IgG4,” Clin. Exp. Immunol., vol. 82, pp. 574-578, 1990.
[45] S. E. Nagy, M. M. Nadia, M. M. Azza, M. Naema, and Z. R. Maha, "Protection against oxidative damage induced by S. mansoni using susceptible/resistant nucleoproteins from Biomphalaria Alexandria,” Asian J. of Biol. Sc., vol. 4, pp. 445-456, 2011.
[46] I. D. Kerr, I. J. Farady, C. J. Marion, R. Rickert, M. M. Sajid, K. C. Pandey, C. R. Caffrey, J. Legac, E. Hansell, J. H. Meckerrow, C. S. Craik, P. J. Rosenthal, and L. S. Brinen, "Vinyl sulfones as antiparasitic agents and a structural basis for drug design,” J. Biolog. Chem., vol. 28, pp. 25697-25703, 2009.